View source for 8jr0


==Cryo-EM structure of Mycobacterium tuberculosis ATP synthase in complex with TBAJ-587==
<StructureSection load='8jr0' size='340' side='right'caption='[[8jr0]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8jr0]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8JR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JR0 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8jr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jr0 OCA], [https://pdbe.org/8jr0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jr0 RCSB], [https://www.ebi.ac.uk/pdbsum/8jr0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jr0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ATPG_MYCTU ATPG_MYCTU] Produces ATP from ADP in the presence of a proton gradient across the membrane. The gamma chain is believed to be important in regulating ATPase activity and the flow of protons through the CF(0) complex.
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== Publication Abstract from PubMed ==
Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase(1,2). However, BDQ also inhibits human ATP synthase(3). At present, how these compounds interact with either M. tuberculosis ATP synthase or human ATP synthase is unclear. Here we present cryogenic electron microscopy structures of M. tuberculosis ATP synthase with and without BDQ and TBAJ-587 bound, and human ATP synthase bound to BDQ. The two inhibitors interact with subunit a and the c-ring at the leading site, c-only sites and lagging site in M. tuberculosis ATP synthase, showing that BDQ and TBAJ-587 have similar modes of action. The quinolinyl and dimethylamino units of the compounds make extensive contacts with the protein. The structure of human ATP synthase in complex with BDQ reveals that the BDQ-binding site is similar to that observed for the leading site in M. tuberculosis ATP synthase, and that the quinolinyl unit also interacts extensively with the human enzyme. This study will improve researchers' understanding of the similarities and differences between human ATP synthase and M. tuberculosis ATP synthase in terms of the mode of BDQ binding, and will allow the rational design of novel diarylquinolines as anti-tuberculosis drugs.

Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587.,Zhang Y, Lai Y, Zhou S, Ran T, Zhang Y, Zhao Z, Feng Z, Yu L, Xu J, Shi K, Wang J, Pang Y, Li L, Chen H, Guddat LW, Gao Y, Liu F, Rao Z, Gong H Nature. 2024 Jul;631(8020):409-414. doi: 10.1038/s41586-024-07605-8. Epub 2024 , Jul 3. PMID:38961288<ref>PMID:38961288</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8jr0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Gong H]]
[[Category: Lai Y]]
[[Category: Liu F]]
[[Category: Rao Z]]
[[Category: Zhang Y]]